ABSTRACT
Protein design tests our understanding of how protein sequence relates to structure and function, that is, our progress toward addressing the informational aspect of the protein-folding problem. In addition, successful protein design exercises provide tools, concepts, and rules for (1) engineering existing protein scaffolds (an area that we refer to as protein engineering or protein redesign) and (2) creating altogether new protein structures and functions (de novo protein design). This second endeavor is the ultimate quest for some protein designers, but it is difcult and,
CONTENTS
11.1 Protein Redesign and Design ........................................................................ 275 11.2 Early Combinatorial Studies Aimed at Repacking the Cores of Proteins .... 277
11.2.1 Repacking the Cores of Natural Proteins ......................................... 277 11.2.2 Creating Novel Proteins Using Binary Patterns of Hydrophobic
and Polar Amino Acids .................................................................... 278 11.3 Phage Display in Engineering Protein Stability ........................................... 279
11.3.1 Nonprotease-Based Applications ...................................................... 279 11.3.2 Combining Phage Display and Proteolysis in Protein
Engineering and Design ...................................................................280 11.4 Worked Example: Repacking the Hydrophobic Core of Ubiquitin .............. 283
11.4.1 Following Protease Selection by Surface Plasmon Resonance ........284 11.4.2 Preparative Protease Selection from Phage-Displayed Libraries .....288
